In:
Food & Function, Royal Society of Chemistry (RSC)
Abstract:
Inhibition of ferroptosis in intestinal epithelial cells serves as an attractive target for the development of therapeutic strategies for colitis. Pinobanksin, one of the main flavonoids derived from propolis, possesses significant anti-inflammatory effects and inhibits cell death of several cell lines. Here, we evaluated whether pinobanksin influenced colitis by modulation of epithelial ferroptosis. Mice treated with 2.5% DSS dissolved in sterile distilled water were established for an acute colitis model. Mitochondrial morphology, colonic iron level, lipid peroxidation products MDA/4-HNE, and lipid reactive oxygen species levels were measured to assess ferroptosis in epithelial cells. RNA_seq and functional analyses were performed to reveal key genes mediating pinobanksin-exerted modulation of ferroptosis. We found that pinobanksin, at different doses, induced significant anti-colitis effects and inhibited the elevated ferroptosis in colonic epithelial cells isolated from DSS-treated mice. Furthermore, RNA_seq assays indicated that pinobanksin significantly increased the cystine transporter SLC7A11 in colonic tissues from colitis mice. Depletion of SLC7A11 largely blocked pinobanksin-induced promotion of cystine uptake/glutathione biosynthesis and consequent suppression of ferroptosis in epithelial cells from colitis mice. Taken together, pinobanksin alleviated DSS-induced colitis largely by inhibition of ferroptosis in epithelial cells. Activation of SLC7A11 by pinobanksin resulted in promotion of cystine uptake, enhancement of glutathione biosynthesis, and suppression of epithelial ferroptosis.
Type of Medium:
Online Resource
ISSN:
2042-6496
,
2042-650X
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2024
detail.hit.zdb_id:
2578152-2
SSG:
21
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